: Action potentials of electrogenic cells, such as neurons and cardiomyocytes, are crucial for their physiological functions. Neurons use action potential to transmit signals over long distances, and cardiomyocytes use action potentials to synchronize the contraction of millions of cells during each heartbeat. To understand these important physiological functions, one of the most important tactics is to accurately record the electrical potentials from cells. However, the current two major classes of electrophysiological methods, intracellular and extracellular recording, suffer severe limitations in their applications. Intracellular recording such as patch clamp suffers from extremely low throughput and toxic intracellular dialysis. Extracellular recording such as planar electrode array suffers from poor signal and lack of one-to-one cell-to-electrode coupling. In the last decade, much effort has been focused on developing new generation of electrophysiology tools to achieve high throughput intracellular recording. In particular, nanotechnology-based electrode sensors developed independently in several groups has shown great promise in achieving highly sensitive and high throughput intracellular recording. However, developing these nascent technologies into robust electrophysiological tools would require extensive studies for characterization, validation, and optimization. This proposal aims to develop the nanoelectrode technology into robust electrophysiological tools for biomedical research. When accomplished, this new technology will enable users to (a) perform sensitive, intracellular recording of action potentials from tens to hundreds of individual cells simultaneously; (b) achieve long-term, minimally-invasive recording of the cells for days to weeks; and (c) afford stable culture and recording of the hSC-CMs under optimal environmental conditions.